Invasive Fusariosis in Patients with Hematologic Diseases.

Fusarium species are filamentous fungi widely encountered in nature, and may cause invasive disease in patients with hematologic conditions. Patients at higher risk are those with acute leukemia receiving induction remission chemotherapy or allogeneic hematopoietic cell transplant recipients. In these hosts, invasive fusariosis presents typically with disseminated disease, fever, metastatic skin lesions, pneumonia, and positive blood cultures. The prognosis is poor and the outcome is largely dependent on the immune status of the host, with virtually a 100% death rate in persistently neutropenic patients, despite monotherapy or combination antifungal therapy. In this paper, we will review the epidemiology, clinical manifestations, diagnosis, and management of invasive fusariosis affecting patients with hematologic diseases.

Early versus Late Fluconazole Prophylaxis in Autologous Hematopoietic Cell Transplantation.

Candidemia is a major complication in hematopoietic cell transplantation (HCT), and antifungal prophylaxis with fluconazole decreases the incidence of this complication. We compared 2 strategies for fluconazole prophylaxis in patients with hematologic malignancy undergoing autologous HCT between 1997 and 2017. From 1997 to 2003, fluconazole prophylaxis (400 mg/d) was given to all HCTs, started with the conditioning regimen (early prophylaxis), and given until neutrophil engraftment or the need of non-prophylactic antifungal therapy. From 2004 on, fluconazole (400mg daily) was started only if (and when) the patient developed oral mucositis (late prophylaxis). Among 571 HCT, 270 received early prophylaxis, 112 received late prophylaxis, and 189 did not receive fluconazole because they did not develop oral mucositis. The incidence of candidemia was 1.8% in the early prophylaxis group, 0% in the late prophylaxis group, and 1.1% in the no prophylaxis group (P = .31). Among patients receiving fluconazole, the median duration of prophylaxis was 17 days (range, 6-36 days) in the early prophylaxis group and 6 days (range, 2-16 days) in the late prophylaxis group (P < .001). The initiation of fluconazole prophylaxis guided by the occurrence of oral mucositis (late prophylaxis) was as good as early fluconazole prophylaxis.

Secular trends of candidemia at a Brazilian tertiary care teaching hospital

ABSTRACT Background Candidemia is the most frequent invasive fungal disease in hospitalized patients, and is associated with high mortality rates. The main objective of this study was to evaluate changes in the epidemiology of candidemia at a tertiary care hospital in a 21-year period. Methods We evaluated all episodes of candidemia diagnosed between 1996 and 2016 at a University-affiliated tertiary care hospital in Brazil. We arbitrarily divided the study period in 3: 1996-2002 (period 1), 2003-2009 (period 2) and 2010-2016 (period 3). Incidence rates were calculated using hospital admissions as denominator. Results We observed 331 episodes of candidemia. The incidence was 1.30 episodes per 1000 admissions, with no significant change over time. Candida albicans (37.5%), C. tropicalis (28.1%), C. parapsilosis (18.4%) and C. glabrata (6.9%) were the most frequent species. The proportion of patients receiving treatment increased (65.5%, 79.4% and 74.7% in periods 1, 2 and 3, respectively, p= 0.04), and the median time from candidemia to treatment initiation decreased from 4 days in period 1 (range 0-32 days) to 2 days in period 2 (range 0-33 days) and 2 days in period 3 (range 0-14 days, p< 0.001). We observed a significant decrease in the use of deoxycholate amphotericin B (47.4%, 14.8% and 11.9%), and an increase in the use of echinocandins (0%, 2.8% and 49.1%; p< 0.001). The APACHE II score increased over time (median 16, 17.5, and 22, p< 0.001). The overall 30-day mortality was 58.9%, and did not change significantly over the study period. Conclusions There was an improvement in patient care, with an increase in the proportion of patients receiving treatment and a decrease in the time to treatment initiation, but no improvement in the outcome, possibly because the proportion of sicker patients increased over time.

Respiratory Tract Infection Caused by Fonsecaea monophora After Kidney Transplantation.

Fonsecaea spp. are melanized fungi which cause most cases of chromoblastomycosis. The taxonomy of this genus has been revised, now encompassing four species, with different pathogenic potential: F. pedrosoi, F. nubica, F. pugnacius, and F. monophora. The latter two species present wider clinical spectrum and have been associated with cases of visceral infection, most often affecting the brain. To our knowledge, this is the first report of proven case of F. monophora respiratory tract infection. A Brazilian 57-year-old-female patient underwent kidney transplantation on January 12, 2013. On the fourth postoperative month, the patient presented with fever, productive cough, and pleuritic pain in the right hemithorax. A thoracic CT scan showed a subpleural 2.2-cm nodular lesion in the right lung lower lobe, with other smaller nodules (0.5-0.7 cm) scattered in both lungs. Bronchoscopy revealed a grayish plaque on the right bronchus which was biopsied. Microscopic examination demonstrated invasion of bronchial mucosa by pigmented hyphae. Culture from the bronchial biopsy and bronchoalveolar lavage samples yielded a melanized mold, which was eventually identified as F. monophora. She started treatment with voriconazole (400 mg q.12h on the first day, followed by 200 mg q.12h). After 4 weeks of therapy, voriconazole dose was escalated to 200 mg q.8h and associated with amphotericin B (deoxycolate 1 mg/kg/day) because of a suspected dissemination to the brain. The patient eventually died of sepsis 8 weeks after the start of antifungal therapy. In conclusion, F. monophora may cause respiratory tract infection in solid organ transplant recipients.

Antimold Prophylaxis May Reduce the Risk of Invasive Fusariosis in Hematologic Patients with Superficial Skin Lesions with Positive Culture for Fusarium.

Hematologic patients with superficial skin lesions on admission growing Fusarium spp. are at a high risk for developing invasive fusariosis during neutropenia. We evaluated the impact of primary prophylaxis with a mold-active azole in preventing invasive fusariosis in these patients. Between August 2008 and December 2014, patients with acute leukemia or aplastic anemia and recipients of hematopoietic cell transplants were screened on admission with dermatologic and direct exams and fungal cultures of superficial skin lesions. Until November 2009, no interventions were made. Beginning in December 2009, patients with baseline skin lesions and a direct exam and/or culture suggestive of the presence of Fusarium spp. received prophylaxis with voriconazole or posaconazole. Skin lesions in the extremities (mostly onychomycosis and interdigital intertrigo) were present on admission in 88 of 239 episodes (36.8%); 44 lesions had hyaline septate hyphae identified by direct exam, and cultures from 11 lesions grew Fusarium spp. Antimold prophylaxis was given for 20 episodes (voriconazole for 17 and posaconazole for 3). Invasive fusariosis was diagnosed in 14 episodes (5.8%). Among patients with baseline skin lesions with positive cultures for Fusarium spp., 4 of 5 without antimold prophylaxis developed invasive fusariosis versus 0 of 6 with antimold prophylaxis (P = 0.01; 95% confidence interval for the difference between proportions, 22% to 96%). Primary antifungal prophylaxis with an antimold azole may prevent the occurrence of invasive fusariosis in high-risk hematologic patients with superficial skin lesions on admission growing Fusarium spp.

Superficial skin lesions positive for Fusarium are associated with subsequent development of invasive fusariosis.

OBJECTIVES: To evaluate the frequency of skin colonization by Fusarium spp. in high-risk hematologic patients and its impact on the subsequent development of invasive fusariosis. METHODS: We screened all high-risk hematologic patients from August 2008 to December 2009 with cultures of 6 pre-defined areas in the feet and hands on admission and at discharge. In addition, cultures of any skin lesion present on admission were performed. RESULTS: Among 61 patients screened, alterations in the skin and/or nails were present in 32 patients (52%) on admission, mostly represented by abnormal appearing nails and intertrigo. Four patients (7.2%) presented positive baseline cultures for Fusarium spp., all in existing lesions of onychomycosis, intertrigo or both. Invasive fusariosis was diagnosed in six patients. The presence of a skin lesion at baseline that grew Fusarium spp. was associated with the subsequent development of invasive fusariosis (p = 0.04). CONCLUSIONS: Our data suggest that: 1) baseline cultures in patients without alterations in the skin and/or nails seems not justifiable; 2) cultures of pre-existing lesions may help to identify a group of patients at higher risk to develop invasive fusariosis. The use of anti-mould prophylaxis in this setting should be explored in future studies.

Increased incidence of invasive fusariosis with cutaneous portal of entry, Brazil.

Invasive fusariosis (IF) is an infection with Fusarium spp. fungi that primarily affects patients with hematologic malignancies and hematopoietic cell transplant recipients. A cutaneous portal of entry is occasionally reported. We reviewed all cases of IF in Brazil during 2000-2010, divided into 2 periods: 2000-2005 (period 1) and 2006-2010 (period 2). We calculated incidence rates of IF and of superficial infections with Fusarium spp. fungi identified in patients at a dermatology outpatient unit. IF incidence for periods 1 and 2 was 0.86 cases versus 10.23 cases per 1,000 admissions (p<0.001), respectively; superficial fusarial infection incidence was 7.23 versus 16.26 positive cultures per 1,000 superficial cultures (p<0.001), respectively. Of 21 cases of IF, 14 showed a primary cutaneous portal of entry. Further studies are needed to identify reservoirs of these fungi in the community and to implement preventive measures for patients at risk.